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1,25(OH)2D3 decreases leptin, IL‐6 and SAA expression in human adipocytes: role of vitamin D receptor
Author(s) -
Lee MiJeong,
Nimitphong Hataikarn,
Guo Weimin,
Holick Michael F,
Fried Susan K
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.48.8
Subject(s) - medicine , adipokine , endocrinology , adipose tissue , calcitriol receptor , leptin , adiponectin , vitamin d and neurology , leptin receptor , inflammation , adipocyte , chemistry , insulin resistance , biology , obesity
Low vitamin D status is associated with human obesity, and higher risk for insulin resistance and development of Type 2 Diabetes. Vitamin D has anti‐inflammatory effects in macrophages and recent studies proposed a role of vitamin D in adipose tissue inflammation and adipokine expression. To test the effects of 1,25(OH)2D3 on adipokine secretion, human adipose tissue explants were cultured with or without 1,25(OH)2D3 (10–8 M). 1,25(OH)2D3 decreased mRNA levels and secretion of leptin, IL‐6, and SAA by 40–50% without affecting MCP‐1 and adiponectin expression. To test direct effects of 1,25(OH)2D3 on adipocytes, we also tested its effects in human adipocytes in culture. Similar to adipose tissue explants, 1,25(OH)2D3 (10–8 M) decreased leptin and IL‐6 by 50–60% in primary human adipocytes in culture, demonstrating the effects of 1,25(OH)2D3 at the level of adipocytes. Using RNAi, we further assessed whether the effects of 1,25(OH)2D3 on adipokines were mediated through the vitamin D receptor (VDR). When VDR protein levels were reduced (>;80% knockdown), 1,25(OH)2D3 did not affect leptin and IL‐6 secretion, demonstrating the effects of 1,25(OH)2D3 are mediated through the VDR. Overall, these results demonstrate that vitamin D has anti‐inflammatory actions in human adipose tissue and adipocytes, and suggest this mechanism may link higher vitamin D status with reduced risk of T2D found in epidemiological studies.